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faculty: "FNWI" and publication year: "2012"
| Author||M.A. Boks|
|Title||Modulation of immune tolerance: the role of tolerogenic dendritic cells and TNFα|
|Promotor||S.M. van Ham|
|Co-promotors||J.A. ten Brinke, J.J. Zwaginga|
|Faculty||Faculty of Science|
|Institute/dept.||FNWI: Swammerdam Institute for Life Sciences (SILS)|
|Keywords||tolerance induction; anti-TNFα-biologicals; regulatory T cells; IL-10; tolerogenic dendritic cells|
|Abstract||This thesis describes the role of tolerogenic DC and anti-TNFα agents in tolerance induction. IL-10-generated tDC potently induce Treg, while inhibiting CD4+ T cell proliferation and cytokine production by Th1 and Th2 cell subsets. Anti-TNFα shares this dual function; inducing IL-10 production and a regulatory phenotype and function in naïve CD4+ T cells, and at the same time counteracting CD4+ effector T cell priming by inhibiting activation status, survival and IFNγ production. Anti-TNFα upregulates inhibitory molecules galectin-3, legumain, GARP and LAG-3 which may be involved in (cell contact-dependent) suppressive function, as is described for natural Treg. In addition, chemokine and chemokine receptor expression are altered after TNFα neutralization, suggesting a change in chemoattraction by Treg and chemotaxis of Treg, thereby regulating the encounter with other immune cells. The picture emerges that tDC and anti-TNFα agents synergistically enhance immune suppression. Combination therapy of tDC and anti-TNFα agents may therefore improve tolerance induction therapy in patients with TNFα-mediated inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, multiple sclerosis and inflammatory bowel diseases.|
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